Contributed by Anna Woodard, MD and Larry Nichols, MD
This 48-year-old white female had a history of an appendectomy and hysterectomy for uterine fibroids. She developed persistent fevers and fatigue, loss of appetite and a 20-pound weight loss over approximately 3 months. On admission to an outside hospital, she was pancytopenic and a computerized tomography scan revealed hepatosplenomegaly. She had persistent fevers but a thorough infectious disease and rheumatologic work up was negative. Liver biopsy showed minimal fibrosis. The patient was transferred to a referral hospital. On admission, she was febrile and tachycardic, with jaundice and a mildly distended abdomen with tenderness in the upper quadrants. No palpable lymphadenopathy was noted. She had anemia (hemoglobin 9 g/dl) and thrombocytopenia (platelets 32,000/cu mm). Liver enzymes were mildly elevated but bilirubin was normal. Computerized tomography showed hepatosplenomegaly and anasarca.
Bone marrow biopsy showed moderately hypercellular bone marrow with trilineage hematopoiesis and abundant stainable iron. Peripheral blood smear showed microcytic anemia and thrombocytopenia. Urine immunoelectrophoresis revealed a monoclonal protein with a small lambda band, however, repeat urine electrophoresis was negative for a monoclonal gammopathy and FISH studies were negative for plasma cell abnormalities. The patient underwent splenectomy. The spleen was severely enlarged, weighing 924 grams. Histologic sections revealed an S-100 positive histiocytic proliferation (Figures 1 and 2). Erythrophagocytosis was also identified (Figure 2). Plasmacytosis was also seen, but kappa and lambda stains revealed a polytypic population (Figure 3). Flow cytometric immunophenotypic studies were suboptimal, but did not reveal any aberrant lymphoid populations. These findings raised the possibility of macrophage activation syndrome (hemophagocytic syndrome) and she was started on steroid therapy and underwent plasmapheresis.
The patient continued to have fevers, became ventilator-dependent and developed acute renal failure. Her lactate dehydrogenase was elevated at 747 U/L and bilirubin rose to 2 mg/dL. She was anemic with a hemoglobin of 7.2 g/dL and profoundly thrombocytopenic (platelets 3,000/cu mm). Blood cultures grew Candida species. The patient was in persistent, apparently septic shock on multiple vasopressors and she died. An autopsy was performed. The following results were found (Figures 4 and following):